Prothrombin Complex Concentrate for Critical Bleeding

OBJECTIVE: To review the evidence supporting the use of prothrombin complex concentrate (PCC) as a hemostatic agent in individuals without hemophilia. DATA SOURCES: Articles were identified through a search of Ovid/MEDLINE (up to April 2011) and Cochrane Central Register of Controlled Trials (up to April 2011). The search terms used were prothrombin complex concentrate, hemorrhage, and bleeding. STUDY SELECTION AND DATA EXTRACTION: The search was limited to comparative studies. Bibliographies of retrieved articles were reviewed to obtain additional articles. The intent of the search was to identify original research comparing PCC to fresh frozen plasma (FFP) or recombinant factor VIIa for the management of bleeding in patients without hemophilia. DATA SYNTHESIS: PCCs are recommended as an alternative to FFP and recombinant factor VIIa for the treatment of serious or life-threatening bleeding related to vitamin K antagonist therapy. Studies in this setting have shown that PCCs are safe and effective and provide prompt reduction of international normalized ratio (INR) compared to FFP. However, most trials are uncontrolled, and the primary outcomes in these studies have been INR reduction rather than hemostatic effect. Other common off-label uses include coagulopathy due to hepatic failure and traumatic hemorrhage; however, there is insufficient evidence to support use of PCC in these settings. Advantages of PCC include the low drug volume required compared to FFP. The use of PCC may be associated with thromboembolic complications. CONCLUSIONS: PCC is a safe and effective alternative to FFP and provides rapid reversal of INR in patients on vitamin K antagonist therapy. These agents may be advantageous compared to FFP in patients with volume restrictions. Comparative trials are needed to compare the various PCC products, FPP, and recombinant factor VIIa with regard to clinically significant outcomes such as hemostatic effect.